Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott; Schöll, Michael; Nosheny, Rachel L.; Tosun, Duygu; Donohue, Michael C.; Aisen, Paul S.; Jagust, William J.; Weiner, Michael W.

doi:10.1212/WNL.0000000000002683

Title: Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

Journal Article · Fri Apr 15 00:00:00 EDT 2016 · Neurology

DOI:https://doi.org/10.1212/WNL.0000000000002683· OSTI ID:1379344

Insel, Philip S. ^[1]; Mattsson, Niklas ^[2]; Mackin, R. Scott ^[3]; Schöll, Michael ^[4]; Nosheny, Rachel L. ^[5]; Tosun, Duygu ^[6]; Donohue, Michael C. ^[7]; Aisen, Paul S. ^[7]; Jagust, William J. ^[8]; Weiner, Michael W. ^[6]

Center for Imaging of Neurodegenerative Diseases, San Francisco, CA (United States). Department of Veterans Affairs Medical Center; Univ. of California, San Francisco, CA (United States). Departments of Radiology and Biomedical Imaging; Lund Univ. (Sweden). Clinical Memory Research Unit, Faculty of Medicine
Lund Univ. (Sweden). Clinical Memory Research Unit, Faculty of Medicine; Skane University Hospital (Sweden). Department of Neurology
Center for Imaging of Neurodegenerative Diseases, San Francisco, CA (United States). Department of Veterans Affairs Medical Center; Univ. of California, San Francisco, CA (United States). Dept. of Psychiatry
University of Gothenburg (Sweden). MedTech West and the Department of Clinical Neuroscience and Rehabilitation; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
Center for Imaging of Neurodegenerative Diseases, San Francisco, CA (United States). Department of Veterans Affairs Medical Center
Center for Imaging of Neurodegenerative Diseases, San Francisco, CA (United States). Department of Veterans Affairs Medical Center; Univ. of California, San Francisco, CA (United States). Departments of Radiology and Biomedical Imaging
University of Southern California, Los Angeles, CA (United States). Department of Neurology, Keck School of Medicine
Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Institute; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division

Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ₄₂. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ₄₂. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE: National Institutes of Health (NIH)

Contributing Organization:: For the Alzheimer's Disease Neuroimaging Initiative

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1379344

Journal Information:: Neurology, Vol. 86, Issue 20; ISSN 0028-3878

Country of Publication:: United States

Language:: English

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Cited by: 34 works

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Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study Pérez-Grijalba, Virginia; Arbizu, Javier; Romero, Judith Alzheimer's Research & Therapy, Vol. 11, Issue 1 https://doi.org/10.1186/s13195-019-0549-1	journal	December 2019
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Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer's disease Mattsson, Niklas; Insel, Philip S.; Palmqvist, Sebastian EMBO Molecular Medicine, Vol. 8, Issue 10 https://doi.org/10.15252/emmm.201606540	journal	August 2016
Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease Palmqvist, Sebastian; Insel, Philip S.; Stomrud, Erik EMBO Molecular Medicine, Vol. 11, Issue 12 https://doi.org/10.15252/emmm.201911170	journal	November 2019
Aβ-Positivity Predicts Cognitive Decline but Cognition Also Predicts Progression to Aβ-Positivity Elman, Jeremy A.; Panizzon, Matthew S.; Gustavson, Daniel E. https://doi.org/10.1101/523787	posted_content	September 2019
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